Pathogenic atrophy refers to the shrinking or wasting away of cells, tissues, or organs due to disease or injury. It's a decrease in size caused by a loss of stimulus or functionality, unlike physiological atrophy which is a normal process like aging. Several factors contribute to pathogenic atrophy, including:
Causes of Pathogenic Atrophy
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Loss of nerve stimulation: This is seen in conditions like spinal muscular atrophy (SMA) or Guillain-Barré syndrome (GBS), where damage to the nerves supplying a muscle leads to its shrinkage. [Reference: Pathologic atrophy is characterized as the loss of stimulus to a specific region (e.g., aging). Neurogenic atrophy results from damage to the nerve innervating a muscle (e.g., SMA, GBS).]
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Decreased blood supply (Ischemia): Reduced blood flow deprives tissues of oxygen and nutrients, causing them to atrophy.
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Nutritional deficiencies: Starvation or inadequate intake of essential nutrients prevents cells from functioning properly and maintaining their size. [Reference: Pathologic atrophy is seen with aging, starvation, and diseases such as Cushing disease (because of taking too much medicines called…)]
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Hormonal imbalances: Conditions like Cushing's disease, caused by excessive cortisol levels, can lead to muscle wasting. [Reference: Pathologic atrophy is seen with aging, starvation, and diseases such as Cushing disease (because of taking too much medicines called…)]
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Aging: As we age, cells naturally shrink and lose functionality, contributing to overall atrophy. [Reference: Pathologic atrophy is characterized as the loss of stimulus to a specific region (e.g., aging).]
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Pressure: Persistent pressure on an organ or tissue can restrict blood flow and lead to atrophy.
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Diseases: Various diseases can cause atrophy, for example, in posterior cortical atrophy (PCA), a visual impairment syndrome often caused by Alzheimer's disease pathology. [Reference: Posterior cortical atrophy (PCA) is an understudied visual impairment syndrome most often due to "posterior Alzheimer's disease (AD)" pathology.]
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Genetic factors: Genetic mutations can disrupt cellular processes, resulting in atrophy. Examples include Spinal and Bulbar Muscular Atrophy (Kennedy's disease) caused by a polyglutamine repeat expansion in the androgen receptor gene. [Reference: Spinal and bulbar muscular atrophy, or Kennedy's disease, is an X-linked motor neuron disease caused by polyglutamine repeat expansion in the androgen…]. Also, pathogenic variants in OPA1 cause autosomal dominant optic atrophy. [Reference: Autosomal dominant optic atrophy caused by six novel pathogenic…]. In many diseases, dysregulation of microRNAs is associated with muscle atrophy. [Reference: Dysregulation of Muscle-Specific MicroRNAs as Common…].
Mechanisms of Pathogenic Atrophy
Several cellular pathways are involved in the process of pathogenic atrophy, including the ubiquitin-proteasome system and the NF-κB pathway. [Reference: Mechanisms have been elucidated for many of these pathways (e.g., ubiquitin-proteasome system, NF-κB, etc.).] Autophagy, a cellular self-cleaning process, also plays a significant role. [Reference: A wide body of evidence has highlighted the involvement and dysregulation of autophagy in SMA. Autophagy is a highly conserved lysosomal degradation process.]
Examples of Pathogenic Atrophy
- Disuse atrophy: Muscle shrinkage due to lack of use, like after a limb injury.
- Neurogenic atrophy: Muscle wasting due to nerve damage.
- Pressure atrophy: Tissue thinning due to sustained pressure, such as bedsores.
- Endocrine atrophy: Organ shrinkage resulting from hormonal deficiencies.
